Lung cancer is a globally highest incident malignancy, and the number of patients is increased by a rate of 3% or more per year due to the environmental and other factors. And 80-85% of the diagnosed patients are attacked by non-small cell lung cancer (NSCLC), wherein, 2%-7% of the patients were induced by the rearrangement of the ALK gene, leading to the accelerated growth of cancer cells and deteriorated conditions. Ceritinib is an oral, selective anaplastic lymphoma kinase (ALK) inhibitor, and in clinical studies, breakthrough progress has been obtained in the treatment of metastatic non-small cell lung cancer (NSCLC) with it. On Apr. 29, 2014, the Food and Drug Administration [FDA] in USA approved the use of Ceritinib for the patients with deteriorated condition after the treatment of Xalkori (crizotinib) or the patients with Xalkori intoleranced and the anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC).
The current disclosed literature [J. Med. Chem. 2013, 56, 5675-5690] discloses a preparation method of Ceritinib (LDK378) as follows:

The synthesis of the key intermediate 4 (2-isopropoxy-5-methyl-4-(piperidin-4-yl) aniline) is a very important synthesis step. According to the literature and the current research results, it has been found that impurities in intermediate 4 will be introduced in the final bulk drug, resulting in that the impurity content is difficult to be limited within 0.1% or less. The quality of intermediate 4 is therefore critical to the quality of the final bulk drug. Thus, purification of intermediate 4 is essential, however, the free base form of intermediate 4 is an oily product which cannot be purified by recrystallization, and column chromatography does not meet the requirements of mass production. It is therefore important to find a form by which intermediate 4 can be purified by recrystallization.